Compositions and methods for nanopolymer-based nucleic acid delivery

Abstract

Provided herein are p-GlcNAc nanoparticle/nucleic acid compositions. In one aspect, the p-GlcNAc nanoparticle/nucleic acid compositions comprise deacetylated poly-N-acetylglucosamine lactate derivative nanoparticles less than 500 nm and a nucleic acid. Also, provided herein are methods for administering a nucleic acid to a subject, the method comprising administering to the subject a p-GlcNAc nanoparticle/nucleic acid composition. In certain embodiments, the p-GlcNAc nanoparticle/nucleic acid composition is administered subcutaneously to the subject.

1 . A poly-N-acetylglucosamine nanoparticle/nucleic acid composition comprising poly-N-acetylglucosamine and a nucleic acid, wherein the nanoparticles are between about 5 nm and 500 nm in size, and wherein 60% to 70% of the poly-N-acetylglucosamine is deacetylated. 
     
     
         2 . (canceled) 
     
     
         3 . The composition of  claim 1 , wherein the deacetylated poly-N-acetylglucosamine comprises a deacetylated poly-N-acetylglucosamine lactate derivative. 
     
     
         4 . The composition of  claim 1 , wherein the deacetylated poly-N-acetylglucosamine has been solubilized with an organic acid, mineral acid, or lactic acid. 
     
     
         5 . (canceled) 
     
     
         6 . The composition of  claim 1 , wherein 60% 65% or 70% of the poly-N-acetylglucosamine is deacetylated. 
     
     
         7 - 9 . (canceled) 
     
     
         10 . The composition of  claim 1 , wherein the poly-N-acetylglucosamine is a fiber of 50 to 200 μm in length. 
     
     
         11 . (canceled) 
     
     
         12 . The composition of  claim 1 , wherein at least 50% of the nanoparticles are between about 100 nm and 200 nm in size. 
     
     
         13 - 16 . (canceled) 
     
     
         17 . The composition of  claim 1 , wherein the nucleic acid is DNA. 
     
     
         18 . The composition of  claim 1 , which further comprises an adjuvant. 
     
     
         19 . The composition of  claim 18 , wherein the adjuvant is a cytokine or polyinosinic:polycytidylic acid (“poly I:C”). 
     
     
         20 . (canceled) 
     
     
         21 . A method for providing sustained expression of a nucleic acid in a subject, the method comprising administering to the subject the composition of  claim 1 . 
     
     
         22 . The method of  claim 21 , wherein the subject is a human or a non-human animal. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 21 , wherein the composition is administered subcutaneously, intramuscularly or intravenously. 
     
     
         25 . The method of  claim 24 , wherein the composition is administered subcutaneously. 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 21 , wherein the administration of the composition results in a sustained expression of a nucleic acid in the composition for at least 1 week, at least 2 weeks or at least 4 weeks. 
     
     
         28 - 29 . (canceled) 
     
     
         30 . The method of  claim 21 , wherein the administering is repeated. 
     
     
         31 . A method for administering a nucleic acid to a subject, the method comprising administering to the subject the composition of  claim 18 , wherein the administering of the composition results in a sustained concurrent release of both the nucleic acid and the adjuvant. 
     
     
         32 . A method of making a poly-N-acetylglucosamine nanoparticle/nucleic acid composition comprising:
 (a) adding a base to poly-N-acetylglucosamine to deacetylate 60% to 70% of the poly-N-acetylglucosamine;   (b) adding a mineral acid or organic acid to a form a deacetylated poly-N-acetylglucosamine ammonium salt derivative;   (c) adding a buffer to facilitate dilution; and   (d) adding a nucleic acid, thereby making a poly-N-acetylglucosamine nanoparticle/nucleic acid composition.   
     
     
         33 . The method of  claim 32 , wherein the mineral acid or organic acid is lactic acid. 
     
     
         34 . The method of  claim 32 , wherein the buffer in step (c) is sodium acetate-acetic buffer. 
     
     
         35 . The method of  claim 32 , wherein the nucleic acid has been combined with a salt. 
     
     
         36 . The method of  claim 35 , wherein the salt is sodium sulfate. 
     
     
         37 - 42 . (canceled) 
     
     
         43 . The composition of  claim 1 , wherein the poly-N-acetylglucosamine is derived from microalgae.